1. Field of Invention
A subject of the present invention is thiazole derivatives of general formula (I) described below for preparing a medicament intended for treating or preventing dyskinesias caused by a chemical treatment.
2. Description of the Related Art
Dyskinesias are generally characterized by involuntary or abnormal movement disorders.
Among the dyskinesias, those caused by a chemical treatment are distinguished. In this case, within the meaning of the present invention, the terms induced dyskinesias or tardive dyskinesias are used, these 2 forms of dyskinesias being dyskinesias caused by a chemical treatment.
Induced dyskinesias: these are induced by a chemical treatment, such as for example in patients treated with L-Dopa which is a dopamine precursor. Patients treated with L-Dopa are generally Parkinsonians, i.e. individuals suffering from Parkinson's disease who present with a pathological deficit of Dopamine as the main characteristic of the disease. Treatment with dopatherapy is absolutely necessary for these patients in order to restore a sufficient level of endogenous dopamine. However, in a significant number of patients it causes severe side effects which are manifested by so-called induced dyskinesias, generally after several years of treatment with L-Dopa. This form of dyskinesia which is a serious undesirable iatrogenic effect of L-Dopa results in particular in the progressive emergence of involuntary movements, muscle rigidity and gait disorders. The emergence of this type of dyskinesia never occurs in “de novo” parkinsonian patients having never previously received treatment with L-Dopa. Unfortunately, at present no satisfactory treatment exists for dyskinesias induced by Dopatherapy. A clinician responsible for a parkinsonian suffering from dyskinesia induced by L-Dopa is then compelled to reduce the daily dose of L-Dopa in order to reduce the severity of the abnormal movements (dyskinesia), which is then accompanied by an aggravation of the blockage phenomena due to Parkinson's disease. The clinician and the patient then have to choose between 2 evils: blockages or dyskinesia.
At present no satisfactory medicinal treatments exist for dyskinesias induced by L-Dopa (a few compounds have been proposed, such as for example yohimbine, idazoxan or amantadine). Only surgical intervention by stimulation of the globus pallidus constitutes a therapeutic strategy which could be effective in the most severe cases, which is clearly not suitable for the majority of patients.
Tardive dyskinesias: these appear tardively in patients receiving long-term treatment with certain medicaments, in particular neuroleptics. By way of example these are patients suffering from schizophrenia treated with the typical neurolopetics (such as for example dopamine D2 receptor agonists) such as haloperidol, or so-called atypical agonists (dopamine D3 or D4 receptor ligands) such as clozapine or olanzepine. These treatments cause so-called tardive dyskinesias as side-effects. These are in particular abnormal involuntary movements, at the facial, oral, lingual, masticatory level, and diffuse movements, rhythmic swinging of the trunk, swaying and stamping;
Thus, the therapeutic treatments known at present are not satisfactory.
In order to respond to the needs of patients, it has become necessary to find a new means for treating these dyskinesias caused by a chemical treatment which are very incapacitating for patients.
Therefore the problem that the invention proposes to solve is to provide a novel compound suited to treating dyskinesias caused by a chemical treatment.